T-cell activation is an immune correlate of risk in BCG vaccinated infants

Helen A. Fletcher; Margaret A. Snowden; Bernard Landry; Wasima Rida; Iman Satti; Stephanie A. Harris; Magali Matsumiya; Rachel Tanner; Matthew K. Oshea; Veerabadran Dheenadhayalan; Leah Bogardus; Lisa Stockdale; Leanne Marsay; Agnieszka Chomka; Rachel Harrington-Kandt; Zita Rose Manjaly-Thomas; Vivek Naranbhai; Elena Stylianou; Fatoumatta Darboe; Adam Penn-Nicholson; Elisa Nemes; Mark Hatheril; Gregory Hussey; Hassan Mahomed; Michele Tameris; J. Bruce McClain; Thomas G. Evans; Willem A. Hanekom; Thomas J. Scriba; Helen McShane

doi:10.1038/ncomms11290

T-cell activation is an immune correlate of risk in BCG vaccinated infants

Helen A. Fletcher, Margaret A. Snowden, Bernard Landry, Wasima Rida, Iman Satti, Stephanie A. Harris, Magali Matsumiya, Rachel Tanner, Matthew K. Oshea, Veerabadran Dheenadhayalan, Leah Bogardus, Lisa Stockdale, Leanne Marsay, Agnieszka Chomka, Rachel Harrington-Kandt, Zita Rose Manjaly-Thomas, Vivek Naranbhai, Elena Stylianou, Fatoumatta Darboe, Adam Penn-NicholsonElisa Nemes, Mark Hatheril, Gregory Hussey, Hassan Mahomed, Michele Tameris, J. Bruce McClain, Thomas G. Evans, Willem A. Hanekom, Thomas J. Scriba, Helen McShane

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Abstract

Vaccines to protect against tuberculosis (TB) are urgently needed. We performed a case-control analysis to identify immune correlates of TB disease risk in Bacille Calmette-Guerin (BCG) immunized infants from the MVA85A efficacy trial. Among 53 TB case infants and 205 matched controls, the frequency of activated HLA-DR + CD4 + T cells associates with increased TB disease risk (OR=1.828, 95% CI=1.25-2.68, P=0.002, FDR=0.04, conditional logistic regression). In an independent study of Mycobacterium tuberculosis-infected adolescents, activated HLA-DR + CD4 + T cells also associate with increased TB disease risk (OR=1.387, 95% CI=1.068-1.801, P=0.014, conditional logistic regression). In infants, BCG-specific T cells secreting IFN- 3 associate with reduced risk of TB (OR=0.502, 95% CI=0.29-0.86, P=0.013, FDR=0.14). The causes and impact of T-cell activation on disease risk should be considered when designing and testing TB vaccine candidates for these populations.

Original language	English
Article number	11290
Number of pages	11
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms11290
Publication status	Published - 12 Apr 2016
Externally published	Yes

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Fletcher, H. A., Snowden, M. A., Landry, B., Rida, W., Satti, I., Harris, S. A., Matsumiya, M., Tanner, R., Oshea, M. K., Dheenadhayalan, V., Bogardus, L., Stockdale, L., Marsay, L., Chomka, A., Harrington-Kandt, R., Manjaly-Thomas, Z. R., Naranbhai, V., Stylianou, E., Darboe, F., ... McShane, H. (2016). T-cell activation is an immune correlate of risk in BCG vaccinated infants. Nature Communications, 7, Article 11290. https://doi.org/10.1038/ncomms11290

@article{470c71ff292641a2949f5f72e9eeb9d1,

title = "T-cell activation is an immune correlate of risk in BCG vaccinated infants",

abstract = "Vaccines to protect against tuberculosis (TB) are urgently needed. We performed a case-control analysis to identify immune correlates of TB disease risk in Bacille Calmette-Guerin (BCG) immunized infants from the MVA85A efficacy trial. Among 53 TB case infants and 205 matched controls, the frequency of activated HLA-DR + CD4 + T cells associates with increased TB disease risk (OR=1.828, 95% CI=1.25-2.68, P=0.002, FDR=0.04, conditional logistic regression). In an independent study of Mycobacterium tuberculosis-infected adolescents, activated HLA-DR + CD4 + T cells also associate with increased TB disease risk (OR=1.387, 95% CI=1.068-1.801, P=0.014, conditional logistic regression). In infants, BCG-specific T cells secreting IFN- 3 associate with reduced risk of TB (OR=0.502, 95% CI=0.29-0.86, P=0.013, FDR=0.14). The causes and impact of T-cell activation on disease risk should be considered when designing and testing TB vaccine candidates for these populations.",

author = "Fletcher, {Helen A.} and Snowden, {Margaret A.} and Bernard Landry and Wasima Rida and Iman Satti and Harris, {Stephanie A.} and Magali Matsumiya and Rachel Tanner and Oshea, {Matthew K.} and Veerabadran Dheenadhayalan and Leah Bogardus and Lisa Stockdale and Leanne Marsay and Agnieszka Chomka and Rachel Harrington-Kandt and Manjaly-Thomas, {Zita Rose} and Vivek Naranbhai and Elena Stylianou and Fatoumatta Darboe and Adam Penn-Nicholson and Elisa Nemes and Mark Hatheril and Gregory Hussey and Hassan Mahomed and Michele Tameris and McClain, {J. Bruce} and Evans, {Thomas G.} and Hanekom, {Willem A.} and Scriba, {Thomas J.} and Helen McShane",

note = "Funding Information: We thank study participants and their families, the community of Cape Winelands East district, and South African Tuberculosis Vaccine Initiative (SATVI) personnel. We also thank Stephen De Rosa, Barry Bloom, Mike Brennan, Chris Wilson, Stephen Lockhart, Jacqueline Shea, Adrian Hill for providing expert opinion. This work was funded by Aeras and The Wellcome Trust with support from the European Commission Framework 7 programme NEWTBVAC and NORAD. H.M. is a Wellcome Trust Senior Clinical Research Fellow. Work on the Adolescent Cohort Study was supported by a Bill and Melinda Gates Foundation (BMGF) Global Health Grant (OPP1021972) and the National Institutes of Health (RO1-AI087915).",

year = "2016",

month = apr,

day = "12",

doi = "10.1038/ncomms11290",

language = "English",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

Fletcher, HA, Snowden, MA, Landry, B, Rida, W, Satti, I, Harris, SA, Matsumiya, M, Tanner, R, Oshea, MK, Dheenadhayalan, V, Bogardus, L, Stockdale, L, Marsay, L, Chomka, A, Harrington-Kandt, R, Manjaly-Thomas, ZR, Naranbhai, V, Stylianou, E, Darboe, F, Penn-Nicholson, A, Nemes, E, Hatheril, M, Hussey, G, Mahomed, H, Tameris, M, McClain, JB, Evans, TG, Hanekom, WA, Scriba, TJ & McShane, H 2016, 'T-cell activation is an immune correlate of risk in BCG vaccinated infants', Nature Communications, vol. 7, 11290. https://doi.org/10.1038/ncomms11290

TY - JOUR

T1 - T-cell activation is an immune correlate of risk in BCG vaccinated infants

AU - Fletcher, Helen A.

AU - Snowden, Margaret A.

AU - Landry, Bernard

AU - Rida, Wasima

AU - Satti, Iman

AU - Harris, Stephanie A.

AU - Matsumiya, Magali

AU - Tanner, Rachel

AU - Oshea, Matthew K.

AU - Dheenadhayalan, Veerabadran

AU - Bogardus, Leah

AU - Stockdale, Lisa

AU - Marsay, Leanne

AU - Chomka, Agnieszka

AU - Harrington-Kandt, Rachel

AU - Manjaly-Thomas, Zita Rose

AU - Naranbhai, Vivek

AU - Stylianou, Elena

AU - Darboe, Fatoumatta

AU - Penn-Nicholson, Adam

AU - Nemes, Elisa

AU - Hatheril, Mark

AU - Hussey, Gregory

AU - Mahomed, Hassan

AU - Tameris, Michele

AU - McClain, J. Bruce

AU - Evans, Thomas G.

AU - Hanekom, Willem A.

AU - Scriba, Thomas J.

AU - McShane, Helen

N1 - Funding Information: We thank study participants and their families, the community of Cape Winelands East district, and South African Tuberculosis Vaccine Initiative (SATVI) personnel. We also thank Stephen De Rosa, Barry Bloom, Mike Brennan, Chris Wilson, Stephen Lockhart, Jacqueline Shea, Adrian Hill for providing expert opinion. This work was funded by Aeras and The Wellcome Trust with support from the European Commission Framework 7 programme NEWTBVAC and NORAD. H.M. is a Wellcome Trust Senior Clinical Research Fellow. Work on the Adolescent Cohort Study was supported by a Bill and Melinda Gates Foundation (BMGF) Global Health Grant (OPP1021972) and the National Institutes of Health (RO1-AI087915).

PY - 2016/4/12

Y1 - 2016/4/12

N2 - Vaccines to protect against tuberculosis (TB) are urgently needed. We performed a case-control analysis to identify immune correlates of TB disease risk in Bacille Calmette-Guerin (BCG) immunized infants from the MVA85A efficacy trial. Among 53 TB case infants and 205 matched controls, the frequency of activated HLA-DR + CD4 + T cells associates with increased TB disease risk (OR=1.828, 95% CI=1.25-2.68, P=0.002, FDR=0.04, conditional logistic regression). In an independent study of Mycobacterium tuberculosis-infected adolescents, activated HLA-DR + CD4 + T cells also associate with increased TB disease risk (OR=1.387, 95% CI=1.068-1.801, P=0.014, conditional logistic regression). In infants, BCG-specific T cells secreting IFN- 3 associate with reduced risk of TB (OR=0.502, 95% CI=0.29-0.86, P=0.013, FDR=0.14). The causes and impact of T-cell activation on disease risk should be considered when designing and testing TB vaccine candidates for these populations.

AB - Vaccines to protect against tuberculosis (TB) are urgently needed. We performed a case-control analysis to identify immune correlates of TB disease risk in Bacille Calmette-Guerin (BCG) immunized infants from the MVA85A efficacy trial. Among 53 TB case infants and 205 matched controls, the frequency of activated HLA-DR + CD4 + T cells associates with increased TB disease risk (OR=1.828, 95% CI=1.25-2.68, P=0.002, FDR=0.04, conditional logistic regression). In an independent study of Mycobacterium tuberculosis-infected adolescents, activated HLA-DR + CD4 + T cells also associate with increased TB disease risk (OR=1.387, 95% CI=1.068-1.801, P=0.014, conditional logistic regression). In infants, BCG-specific T cells secreting IFN- 3 associate with reduced risk of TB (OR=0.502, 95% CI=0.29-0.86, P=0.013, FDR=0.14). The causes and impact of T-cell activation on disease risk should be considered when designing and testing TB vaccine candidates for these populations.

UR - http://www.scopus.com/inward/record.url?scp=84964397293&partnerID=8YFLogxK

U2 - 10.1038/ncomms11290

DO - 10.1038/ncomms11290

M3 - Article

C2 - 27068708

AN - SCOPUS:84964397293

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 11290

ER -

T-cell activation is an immune correlate of risk in BCG vaccinated infants

Abstract

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Erratum: T-cell activation is an immune correlate of risk in BCG vaccinated infants (Nature Communications (2016) 7 (11290) DOI: 10.1038/ncomms11290)

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